Sodium Channel SCN3A (Na(V)1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development

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http://hdl.handle.net/10138/314797

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Smith , R S , Kenny , C J , Ganesh , V , Jang , A , Borges-Monroy , R , Partlow , J N , Hill , R S , Shin , T , Chen , A Y , Doan , R N , Anttonen , A-K , Ignatius , J , Medne , L , Bönnemann , C G , Hecht , J L , Salonen , O , Barkovich , A J , Poduri , A , Wilke , M , de Wit , M C Y , Mancini , G M S , Sztriha , L , Im , K , Amrom , D , Andermann , E , Paetau , R , Lehesjoki , A-E , Walsh , C A & Lehtinen , M K 2018 , ' Sodium Channel SCN3A (Na(V)1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development ' , Neuron , vol. 99 , no. 5 , pp. 905-+ . https://doi.org/10.1016/j.neuron.2018.07.052

Title: Sodium Channel SCN3A (Na(V)1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development
Author: Smith, Richard S.; Kenny, Connor J.; Ganesh, Vijay; Jang, Ahram; Borges-Monroy, Rebeca; Partlow, Jennifer N.; Hill, R. Sean; Shin, Taehwan; Chen, Allen Y.; Doan, Ryan N.; Anttonen, Anna-Kaisa; Ignatius, Jaakko; Medne, Livija; Bönnemann, Carsten G.; Hecht, Jonathan L.; Salonen, Oili; Barkovich, A. James; Poduri, Annapurna; Wilke, Martina; de Wit, Marie Claire Y.; Mancini, Grazia M. S.; Sztriha, Laszlo; Im, Kiho; Amrom, Dina; Andermann, Eva; Paetau, Ritva; Lehesjoki, Anna-Elina; Walsh, Christopher A.; Lehtinen, Maria K.
Contributor: University of Helsinki, Anna-Elina Lehesjoki / Principal Investigator
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Medicum
Date: 2018-09-05
Language: eng
Number of pages: 16
Belongs to series: Neuron
ISSN: 0896-6273
URI: http://hdl.handle.net/10138/314797
Abstract: Channelopathies are disorders caused by abnormal ion channel function in differentiated excitable tissues. We discovered a unique neurodevelopmental channelopathy resulting from pathogenic variants in SCN3A, a gene encoding the voltage-gated sodium channel Na(V)1.3. Pathogenic Na(V)1.3 channels showed altered biophysical properties including increased persistent current. Remarkably, affected individuals showed disrupted folding (polymicrogyria) of the perisylvian cortex of the brain but did not typically exhibit epilepsy; they presented with prominent speech and oral motor dysfunction, implicating SCN3A in prenatal development of human cortical language areas. The development of this disorder parallels SCN3A expression, which we observed to be highest early in fetal cortical development in progenitor cells of the outer subventricular zone and cortical plate neurons and decreased postnatally, when SCN1A (Na(V)1.1) expression increased. Disrupted cerebral cortical folding and neuronal migration were recapitulated in ferrets expressing the mutant channel, underscoring the unexpected role of SCN3A in progenitor cells and migrating neurons.
Subject: REVERSE NA+/CA2+ EXCHANGE
PERISYLVIAN POLYMICROGYRIA
NEURAL PROGENITORS
ALPHA-SUBUNIT
RADIAL GLIA
IN-VITRO
EPILEPSY
NEURONS
CONTRIBUTES
EXPRESSION
3112 Neurosciences
3124 Neurology and psychiatry
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